Molero-Leal M
Instituto de Investigaciones Biológicas, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
Invest Clin. 1998 Jun;39(2):125-54.
In recent years, nitric oxide (NO), a single but highly reactive molecule has become known as the central point of many researchs. NO is synthesized by the enzyme nitric oxide synthase (NOS) in mammals from the amino-acid L-arginine. The products of L-arginine oxidation by NOS are L-citrulline and NO. Nitric oxide has a very short half life, is lipid soluble, reacts easily with several enzymatic systems, and is produced by a wide amount of cells. At least, three kinds of enzymes NOS have been described: two of them are calcium-dependent and continuously present in select cells (constitutive NOS, cNOS). One cNOS isoform is present in the cytosol of neuronal cells, while the other isoform is present in membrane-bound form, in endothelial cells. cNOS produces small quantities of NO, following stimulation by specific agonist. NO produced by cNOS frequently mediates cellular communications and cellular signaling. A third isoform is calcium-independent, is not present in unstimulated cells, and produces large quantities of NO following stimulation of the appropriate cell with cytokines or LPS (inducible NOS, iNOS). NO is a mediator of both physiological and pathological process. It acts directly on its targets, one of them, maybe the most important, is the soluble guanylate cyclase, and produces a variety of biological effects, ranged from cytoprotection to cytotoxicity. An analysis of the biochemistry and physiology of NO is the focus of this review, together with its biological action and potential therapeutical implications.
近年来,一氧化氮(NO),一种简单但高度反应性的分子,已成为许多研究的核心。在哺乳动物中,NO由一氧化氮合酶(NOS)从氨基酸L-精氨酸合成。NOS氧化L-精氨酸的产物是L-瓜氨酸和NO。一氧化氮半衰期很短,脂溶性,容易与多种酶系统反应,并且由大量细胞产生。至少已描述了三种NOS酶:其中两种是钙依赖性的,持续存在于特定细胞中(组成型NOS,cNOS)。一种cNOS同工型存在于神经元细胞的胞质溶胶中,而另一种同工型以膜结合形式存在于内皮细胞中。cNOS在特定激动剂刺激后产生少量NO。cNOS产生的NO经常介导细胞通讯和细胞信号传导。第三种同工型是钙非依赖性的,不存在于未受刺激的细胞中,在用细胞因子或LPS刺激适当细胞后产生大量NO(诱导型NOS,iNOS)。NO是生理和病理过程的介质。它直接作用于其靶标,其中之一可能是最重要的,是可溶性鸟苷酸环化酶,并产生多种生物学效应,从细胞保护到细胞毒性。对NO的生物化学和生理学分析是本综述的重点,以及其生物学作用和潜在的治疗意义。